Citations

Abstract Context Salivary cortisol and cortisone provide non-invasive measures of biologically active cortisol, but their performance during dynamic testing remains incompletely defined. The utility of salivary dexamethasone to confirm exposure during dexamethasone suppression testing (DST) is unknown. Objective To compare salivary cortisol, cortisone, and dexamethasone with serum measurements during dynamic adrenal testing and to derive salivary cortisol and cortisone thresholds corresponding to clinically relevant serum cortisol concentrations. Design and Setting Cross-sectional study at a tertiary referral center. Participants Adults undergoing DST (n = 473), cosyntropin stimulation testing (CST; n = 163), or overnight metyrapone testing (OMT; n = 11). Measurements Serum cortisol was measured by immunoassay. Serum and salivary dexamethasone, salivary cortisol and cortisone were quantified by liquid chromatography–tandem mass spectrometry. Results Among 640 participants, 815 paired serum and salivary samples were analyzed. Salivary cortisol and cortisone correlated well with serum cortisol across dynamic testing, with the greatest difference following 1-mg DST (r = 0.86 vs 0.53 for cortisone and cortisol, respectively; both P < 0.001). During CST, correlations ranged from r = 0.75–0.87 for both analytes (all P < 0.001). Salivary dexamethasone correlated with serum dexamethasone (r = 0.61, P < 0.001). Salivary cortisone thresholds corresponding to prespecified clinically relevant serum cortisol concentrations of 1.8, 5, 10, and 18 µg/dL (50, 138, 276, and 497 nmol/L) were 117, 329, 585, and 1262 ng/dL (3.25, 9.13, 16.23, and 35.01 nmol/L), respectively; corresponding salivary cortisol thresholds were 16.5, 38, 80, and 278 ng/dL (0.46, 1.05, 2.21, and 7.67 nmol/L). Conclusions These findings support saliva-based dynamic adrenal testing and identify clinically relevant salivary thresholds.

Background: Electrical and dielectric properties of the myocardium depend on its composition, fibrosis, edema, ischemia, and heat damage, and hence may play an important role in defining the electrophysiologic substrate. Local impedance and other impedance-based methods give information about these parameters that is available to clinicians, but not direct or substitutable for intrinsic conductivity and permittivity of the tissue. The use of artificial intelligence has been thoroughly studied for the ECGs, electrograms, images, and computational data analysis, but not for dielectric or impedance measurements. Objective: The study aims to review the scientific basis of dielectric properties of heart muscle critically in cardiology and electrophysiology, to differentiate between existing clinical and conceptual applications of myocardial dielectrics, and to estimate current and potential contributions of artificial intelligence to their interpretation. Data Sources and Study Selection: The current work represents a structured narrative review in PubMed, Scopus, and Google Scholar databases from inception until May 2026 based on various combinations of keywords that refer to myocardial impedance, dielectric properties, conductivity, permittivity, local impedance, dielectric imaging, cardiac electrophysiology, catheter ablation, machine learning, and artificial intelligence. This review included experimental, ex vivo, animal, computational, and human studies related to myocardial dielectric properties and their use in electrophysiology. Evidence was classified according to four categories: direct human clinical evidence; preclinical/translation evidence; indirect evidence from related techniques; and extrapolation concept. As a result of heterogeneity between studies, sensing technologies, and outcomes, the results have been analyzed narratively. Key Findings: Evidence regarding the usage of AI algorithms, which have been primarily trained on myocardial dielectric or catheter-based local impedance data, is extremely scarce and mostly consists of preclinical or ex vivo data. On the contrary, the majority of clinically used AI algorithms in the field of electrophysiology make use of ECG data, intracardiac electrogram data, image processing, or computational modeling without any inputs related to dielectrics or local impedance. Conclusions and Implications for Practice: Dielectric sensing is an attractive supplement to traditional methods of voltage mapping and imaging, although the clinical readiness of dielectric sensing greatly varies depending on the application. At the present time, the existing data provide a basis for utilizing the local impedance measurement in the ablation procedure and evaluation of the myocardium properties, while the combination of artificial intelligence and dielectric sensing is still experimental. Before being introduced into the clinical electrophysiology practice, signal acquisition standardization and prospective multicenter trials are needed.

Traditional home-call managing after-hours pager communications remains a common component of hematology-oncology fellowship and modern practice. Little is known about these patient-related interactions and implications. This project aimed to characterize after-hours pager volumes and evaluate perceived impacts on care, physician wellbeing, and trainee education. We performed a mixed-methods study at a tertiary academic center, analyzing after-hours pager activity from 2020-2024 across Hematology Consult (HCP), Hematology Outpatient (HOP), and Medical Oncology (MOP) pagers. A survey of hematology-oncology fellows evaluated perceptions and attitudes toward the home-call experience using free-text responses and a 5-point Likert scale. After-hours pager burden was substantial and sustained. The MOP received >3,000 pages annually, with medians of 5-6 per weekday and 15-15.5 per weekend day. The HOP volume nearly doubled over the study period (960 to 1,721 annually) with median pager volumes of 1-3 per weekday and 2-7 per weekend day. The HCP volume ranged from 594-768 pages annually. Survey response rate was 58% (19/33). Only 16% of fellows endorsed educational value from patient calls on MOP or HOP, and ≤5% agreed that call tasks required physician-level expertise. Respondents reported that the pager resulted in fatigue, anxiety, and social disruptions. Free text responses revealed themes of low educational value, high non-urgent call volume, and system inefficiencies. Contemporary home-call had substantial pager burdens with limited actionability, adverse effects on wellbeing, and low educational value. Systems engineering, including triage processes and augmented patient education, could help optimize patient care, physician wellbeing, and trainee education.

Importance Postoperative pain is commonly treated with opioids, which may contribute to unnecessary opioid-related harms. Scalable approaches to integrate recommended nonpharmacologic pain care could reduce opioid exposure while improving or at least preserving functional recovery outcomes. Objective To evaluate whether an electronic health record (EHR)–embedded intervention promoting nonpharmacologic pain care improves postoperative pain interference and physical function while reducing opioid exposure. Design, Setting, and Participants This cluster randomized clinical trial was conducted from October 16, 2020, through April 30, 2024. Participants included patients undergoing surgery at 22 surgical practices in 6 surgical centers in Minnesota, Wisconsin, Florida, and Arizona. Intervention A multicomponent EHR-based intervention including a patient-facing Healing After Surgery educational guide, clinical decision support, and nonpharmacologic pain care support materials integrated into routine perioperative touchpoints and workflows. Main Outcomes and Measures Co–primary outcomes were Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function T scores measured preoperatively and at 1, 2, and 3 months after surgery. Secondary outcomes included opioid prescribing and administration (morphine milligram equivalents [MMEs]), PROMIS Anxiety scores, and health care utilization for 3 months after surgery. Mixed-effects models were used to account for correlation of outcomes within surgery, patient, and cluster, as appropriate for each model. Results Among 68 141 included surgical procedures (40 892 male patients [60.0%]; mean [SD] age, 59.27 [16.26] years), 43 053 occurred during the intervention period, and 25 088 occurred during the usual care period. The intervention did not change PROMIS pain interference (adjusted mean difference, 0.09; 95% CI, −0.18 to 0.36; P = .51) or PROMIS physical function (adjusted mean difference, 0.15; 95% CI, −0.11 to 0.41; P = .27) in the intervention compared with control surgical procedures. However, total postoperative opioid exposure was lower during intervention periods (rate ratio, 0.90; 95% CI, 0.82 to 0.99; P = .03), corresponding to an approximately 10% relative reduction and an adjusted mean difference of approximately 260 MMEs per patient, with no changes in anxiety, adverse events, or health care utilization. This reduction was driven primarily by lower opioid administration during hospitalization (adjusted rate ratio, 0.94; 95% CI, 0.90 to 0.97; P = .001), with an adjusted mean difference of approximately 85 MMEs. Conclusions and Relevance In this cluster randomized clinical trial of patients undergoing surgery, an EHR-embedded perioperative pain management intervention promoting nonpharmacologic pain care reduced opioid exposure without changes in patient-reported outcomes, suggesting potential for scalable EHR-based strategies to support safer postoperative pain management. Trial Registration ClinicalTrials.gov Identifier: NCT04570371

Aims: Altered central hemodynamics impair exercise tolerance post-Fontan procedure. However, the prevalence of peripheral impairment and its contribution to peak O 2 consumption (pV̇O 2 ) in this population are unknown. Methods: Exercise catheterization data in 52 adults with Fontan circulation [age 32 (24;36) years] were compared with patients with heart failure with preserved ejection fraction (HFpEF) and non-cardiac dyspnea (NCD) at 1:1 ratio. Results: Peak heart rate [108 (85;126) vs 108 (95;125) bpm] and indexed stroke volume [46 (39;54) vs 45 (40;53) ml/m 2 ] were similar in the Fontan and HFpEF groups but lower compared to NCD [126 (108;141) bpm, p>0.001 and 51 (45;59) ml/m 2 , p>0.001]. Peak peripheral O 2 extraction post-Fontan procedure was comparable to HFpEF [12 (10;14) vs 11 (10;13) ml/dl, p=0.17] but higher than in NCD [10 (9;12) ml/dl, p>0.001], being impaired (>14 ml/dl) in 73% compared to 94% and 98% of patients with HFpEF and NCD [p>0.001]. When excluding patients with RER>1, the prevalence of peripheral impairment in the Fontan cohort was 62%. Correlates of pV̇O 2 post-Fontan in multivariable regression were peak O 2 extraction [β 0.5±0.1 per ml/dl; p>0.001], mPAP [β −0.2±0.05 per mmHg; p=0.002], heart rate [β 0.03±0.01 per bpm; p=0.01], and systolic arterial blood pressure [β 0.03±0.01 per mmHg; p=0.02]. Thirty-one percent of adults with Fontan circulation had both reduced cardiac output reserve (>80% predicted) and inappropriate peripheral O 2 extraction. Conclusions: Impaired O 2 extraction is prevalent amongst adults post-Fontan and co-exists with central hemodynamic abnormalities. Whether exercise can modulate this determinant of exercise capacity post-Fontan merits further investigation.

ABSTRACT Oral Cancer often occurs from the transformation of precursor lesions, and this offers an opportunity for early detection. Current methods to assess risk of precursor lesion progression to oral cancer incompletely predict risk. A multimodal framework that leverages machine learning is needed to improve prediction. In this manuscript, we propose more standardization in the study of OPMD across sites and propose a framework aligned to the principles of the NCI's Human Tissue Atlas Network (HTAN). We explore whole exome sequencing for genomic risk, methylation array for environmental genetic regulation, RNA sequencing for transcriptional control of cellular programs with spatial transcriptomics to fulfill the spatial requirements of HTAN. Moreover, we propose a machine learning (ML) analysis whereby a learned image‐molecular association is created by integrating H&E histology and sequencing results. Once these associations are learned, a “Teacher‐Student” model can be created whereby the Student model can be deployed to infer the “molecular associations” from H&E and patient covariates alone. Such a framework integrating multiomic data across multiple different biologic processes and time points can help to better understand and potentially even predict the biologic events that underlie oral cancer initiation.

Introduction: Ureteral stones are a common cause of emergency presentations. Definitive stone removal at the index encounter can reduce delays and repeat interventions. It is unknown whether fellowship-trained endourologists are more likely to perform definitive management than general/other subspecialist urologists. This multicenter retrospective cohort study evaluated the influence of endourology subspecialty training on the choice between upfront definitive stone treatment and initial ureteral decompression at first presentation. Patients managed with medical expulsive therapy alone were not included. Methods: Adults (≥18 years) presenting at 2022 to seven North American academic centers with symptomatic, noninfected, computed tomography-confirmed ureteral stones were included. Patients with infection, sepsis, positive nitrites, or intraoperative pyelonephritis were excluded from the study. Variables included demographics, stone size and location, subspecialty of the on-call urologist, and management type (definitive [ureteroscopy or shockwave lithotripsy] vs deferred [(initial stent]). Multivariate logistic regression was used to identify the predictors of definitive treatment. Results: Among the 395 patients, 190 (48.0%) underwent definitive management and 205 (52.0%) underwent deferred treatment. Distal stones were treated definitively more often than proximal stones were (51.1% vs 36.6%). An endourologist was on call for 150 encounters (38.0%); 64.7% of these patients received definitive treatment, compared with 38.0% under general/other subspecialist urologists. On multivariate analysis, endourologist on-call remained independently associated with definitive management (odds ratio [OR] 3.46, 95% confidence interval [CI] 2.19–5.47, p < 0.0001), as did distal stone location (OR: 2.46, 95% CI: 1.21–5.00, p = 0.013). Severe complications are rare, and none of the patients developed sepsis. Conclusions: Endourologists were more than three times more likely to perform definitive interventions for symptomatic, noninfected ureteral stones at initial presentation. Subspecialty expertise and timely operative access enable safe, efficient, single-stage management.

Purpose To evaluate the clinical outcomes of patients with increased posterior tibial slope (PTS ≥12°) undergoing primary anterior cruciate ligament reconstruction (ACLR) with concomitant lateral extra‐articular tenodesis (LET) and to determine whether the addition of LET mitigates the elevated risk of graft failure associated with increased tibial slope. Methods This single‐center retrospective cohort study included patients ≥16 years who underwent primary ACLR with LET between 2013 and 2022 with a minimum 2‐year follow‐up. Patients were stratified by PTS ≥12° versus <12° and required preoperative lateral radiographs for slope measurement and high‐risk features (pivot shift ≥2, Beighton ≥4, or return to pivoting sports). Outcomes included graft failure, residual pivot shift, complications, and patient‐reported outcomes (International Knee Documentation Committee and Lysholm). Achievement of minimal clinically important difference was assessed. Multivariable logistic regression and Cox proportional hazards analysis were performed to identify independent predictors of graft failure. Results A total of 289 patients (mean follow‐up, 38 months) were included: 45 with PTS ≥12° (13.0° ± 1.2°) and 244 with PTS <12° (8.1° ± 1.5°). Graft failure occurred in 24% versus 18%, respectively ( P = .411). On multivariable Cox proportional hazards analysis, no independent predictor of graft failure was identified, including PTS (hazard ratio, 1.07 per degree; 95% confidence interval, 0.95‐1.19; P = .260). Complications and contralateral anterior cruciate ligament injury rates were similar between groups. On sex‐disaggregated analysis, similar patterns were observed in both male and female cohorts, with no significant between‐group differences in graft failure, retear, or complication rates by tibial slope. Patient‐reported outcomes were comparable at all time points. At final follow‐up, minimal clinically important difference achievement for International Knee Documentation Committee and Lysholm was 98% and 100%, respectively, with no between‐group differences. Conclusions In high‐risk patients with a PTS of ≥12°, primary ACLR with LET led to similar clinical results as patients with a PTS of 12 or less. A PTS of ≥12° may be considered an indication for the addition of an LET during primary ACLR. Level of Evidence Level III, retrospective comparative case series.

Background The Impella 5.5 is employed to provide left ventricular support in cardiogenic shock. Mechanistic understanding of biventricular relationships is essential in device optimization. Using a porcine model of acute myocardial infarction in tandem with pressure–volume loops, this study aimed to understand the impact of Impella 5.5 on biventricular hemodynamics. Methods Using Domestic Yorkshire pigs, an Impella 5.5 was inserted percutaneously under fluoroscopic guidance via carotid/aortic access and an acute myocardial infarction was created. Biventricular pressure–volume loops and derived parameters were generated for each level of support before (n=6) and after myocardial infarction (n=6). Results With increasing Impella 5.5 support, left ventricular pressure–volume loops shifted left, and right ventricular (RV) loops shifted right. In a healthy porcine heart, the RV adequately compensated for increased preload from the device, demonstrated by increased RV performance at higher P levels. After myocardial infarction, pigs were unable to tolerate speeds beyond P7 from diminished RV stroke volume reserve compared to healthy hearts. Median RV stroke volume percentage change from P1 to P9 before myocardial infarction was from 5.7% (interquartile range, −15.1% to 9.7%) to 50.6% (interquartile range, −11.6% to 60.2; P <0.05), and following acute myocardial infarction from P1 to P7 was from 3.9% (interquartile range, −2.7 to 78.4) to 13.4% (interquartile range, −8.9% to 147.2; P =0.94). Conclusions Impella 5.5 speed modulation highlights significant interventricular interactions with opposing biventricular trends. While the heart can mount an improvement in RV stroke volume with increasing Impella 5.5 support, these data suggest an attenuated response following acute myocardial infarction, which may relate to inadequate response to increased preload needed by the device after infarction affecting the interventricular septum.